The identification of genetic factors contributing to human oocytes maturation arrest using whole-genome sequencing

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Abstract

Female fertility is dependent on the successful maturation of oocytes, a complex and meticulously regulated cellular process that prepares oocytes for fertilization and subsequent embryonic development. However, with advancing age and the onset of reproductive senescence, the probability of errors in this process increases significantly. These age-related alterations are associated with the accumulation of genetic and epigenetic abnormalities, mitochondrial dysfunction, and modifications in cytoskeletal function, all of which elevate the risk of oocyte maturation defects, embryonic developmental anomalies, and infertility. In this study, we conducted a genetic analysis of a patient experiencing female infertility due to oocyte maturation arrest and identified a heterozygous variant, c.527C>T (p.Ser176Leu), in the TUBB8 gene. This variant disrupts microtubule formation, leading to defects in meiotic spindle formation and subsequent oocyte arrest. Variants in the TUBB8 gene, which encodes a crucial component of microtubules, have been implicated in the pathogenesis of oocyte maturation arrest, abnormal fertilization, and other related disorders. Such changes may be particularly pronounced in women exhibiting characteristics of reproductive senescence.

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About the authors

N. A. Arakelyan

Sirius University of Science and Technology

Email: manakhov@rogaevlab.ru

Center for Genetics and Life Science

Russian Federation, Sirius, 354340

A. P. Grigorenko

Vavilov Institute of General Genetics, Russian Academy of Sciences

Email: manakhov@rogaevlab.ru
Russian Federation, Moscow, 119991

V. M. Petrova

Sirius University of Science and Technology

Email: manakhov@rogaevlab.ru

Center for Genetics and Life Science

Russian Federation, Sirius, 354340

E. Vasilevskaya

Sirius University of Science and Technology

Email: manakhov@rogaevlab.ru

Center for Genetics and Life Science

Russian Federation, Sirius, 354340

D. V. Islamgulov

Fomin Clinic

Email: manakhov@rogaevlab.ru
Russian Federation, Ufa, 450078

A. V. Dolgikh

Fomin Clinic

Email: manakhov@rogaevlab.ru
Russian Federation, Ufa, 450078

A. D. Manakhov

Sirius University of Science and Technology; Vavilov Institute of General Genetics, Russian Academy of Sciences

Author for correspondence.
Email: manakhov@rogaevlab.ru

Center for Genetics and Life Science

Russian Federation, Sirius, 354340; Moscow, 119991

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2. Fig. 1. Results of Sanger sequencing of the proband and her family members (TUBB8 c.527C>T, p.Ser176Leu).

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